{"gene":"RPS27","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":1993,"finding":"Rat ribosomal protein S27 (RPS27) has 83 amino acids and contains a zinc finger-like motif (C4-type), consistent with zinc-binding and potential DNA/RNA interaction. Ribosomes and ribosomal subunits were shown to contain zinc and iron.","method":"cDNA sequencing, amino acid sequence determination, hybridization analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 (structural/primary structure determination) / Weak — single lab, biochemical characterization without functional mutagenesis of the zinc finger","pmids":["8441676"],"is_preprint":false},{"year":1976,"finding":"RPS27 was isolated and purified from the 40S ribosomal subunit of rat liver ribosomes, establishing it as a bona fide structural component of the small ribosomal subunit.","method":"Ion exchange chromatography, gel filtration, SDS-PAGE, amino acid composition analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical purification and characterization from ribosomes, foundational work replicated in subsequent studies","pmids":["947902"],"is_preprint":false},{"year":2010,"finding":"RPS27 binds to the central acidic domain of MDM2 via its N-terminal region, forming an in vivo triplex with MDM2-p53. RPS27 competes with p53 for MDM2 binding, inhibits MDM2-mediated p53 ubiquitination, and increases p53 levels by extending p53 protein half-life. RPS27 expression is repressed by p53.","method":"Co-immunoprecipitation, domain-mapping pulldown, ubiquitination assay, siRNA knockdown, p53 half-life measurements, reporter assay","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vivo ubiquitination assay, domain mapping, and functional p53 half-life measurements in single study with multiple orthogonal methods","pmids":["21170087"],"is_preprint":false},{"year":2014,"finding":"Loss-of-function frameshift deletion in RPS27 was identified in a Diamond-Blackfan anaemia patient. In vitro knockdown of RPS27 disrupted pre-ribosomal RNA processing. Zebrafish rps27 morphants showed impaired erythrocyte production and developmental defects.","method":"Whole-exome sequencing, in vitro knockdown, pre-rRNA processing assay, zebrafish morpholino knockdown model","journal":"British journal of haematology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined pre-rRNA processing phenotype and in vivo zebrafish model, single lab","pmids":["25424902"],"is_preprint":false},{"year":2014,"finding":"A recurrent hotspot mutation in the 5' UTR of RPS27 (~10% of melanomas) expands the 5'TOP element, a regulatory motif that controls expression of ribosomal protein transcripts in a growth-dependent manner, potentially sensitizing RPS27 mRNA to growth-mediated translational regulation.","method":"Exome sequencing of melanoma cohorts, 5'TOP element functional analysis","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — recurrent mutation identified across independent cohorts with in vitro functional characterization of 5'TOP motif expansion","pmids":["24913145"],"is_preprint":false},{"year":2020,"finding":"Both RPS27 and RPS27L are subjected to neddylation by MDM2 E3 ubiquitin ligase, and deneddylation by NEDP1. Blockage of neddylation with MLN4924 destabilizes RPS27 by shortening its protein half-life. Knockdown of RPS27 sensitizes cancer cells to MLN4924-induced apoptosis, while ectopic RPS27 expression desensitizes cells.","method":"Neddylation assay, protein half-life measurement (CHX chase), siRNA knockdown, ectopic overexpression, apoptosis assay","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct neddylation biochemical assay with identified writer (MDM2) and eraser (NEDP1), single lab with multiple functional readouts","pmids":["32779270"],"is_preprint":false},{"year":2023,"finding":"Rps27 and Rps27l are paralogous ribosomal proteins that arose by vertebrate whole-genome duplication. They have inversely correlated expression across mouse cell types. Rps27- and Rps27l-containing ribosomes preferentially associate with different subsets of mRNAs (specialized ribosomes). Homozygous loss of either is lethal at different developmental stages, but expressing one protein from the other's locus fully rescues lethality, demonstrating the two proteins are functionally equivalent but must achieve appropriate total expression across cell types.","method":"Endogenous protein tagging, ribosome profiling/RNA association, genetic knockin rescue, mouse knockout studies","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — endogenous tagging, ribosome profiling, and definitive genetic rescue experiments with multiple orthogonal approaches in a single rigorous study","pmids":["37306301"],"is_preprint":false},{"year":2025,"finding":"ZAKα (the ribotoxic stress response kinase) directly interacts with RPS27 at the mRNA exit channel of elongating ribosomes, as well as with RACK1 and 18S rRNA helix-26. This interaction is stabilized by mRNA stasis and is part of a mechanism by which ZAKα senses translational impairment to activate p38/JNK signaling.","method":"AlphaFold3 structural prediction, RNA crosslinking and immunoprecipitation (CLIP), biochemical interaction assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CLIP and structural prediction with functional validation, single preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.11.22.689755"],"is_preprint":true},{"year":2019,"finding":"Two recurrent mutations in the RPS27 promoter were associated with decreased RPS27 mRNA levels in vitro in melanoma. Loss-of-function experiments showed that high RPS27 status provides increased proliferative and invasive capacities, while low RPS27 confers survival advantage under low attachment conditions and resistance to therapy.","method":"Targeted sequencing, in vitro reporter assay, loss-of-function (siRNA/shRNA), transwell invasion/proliferation assay","journal":"Pigment cell & melanoma research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — promoter functional assay combined with loss-of-function phenotypic characterization, single lab","pmids":["31663663"],"is_preprint":false},{"year":2022,"finding":"RPS27 overexpression in thyroid cancer cells selectively regulates expression of inflammatory/immune response genes and alternative splicing of genes in the TRIF-dependent toll-like receptor signaling pathway and apoptotic process, as revealed by transcriptome analysis.","method":"RPS27 overexpression, RNA-seq transcriptomics, alternative splicing analysis, qRT-PCR validation","journal":"Advances in clinical and experimental medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single overexpression transcriptomics study without mechanistic follow-up of direct binding or pathway epistasis","pmids":["35546566"],"is_preprint":false},{"year":2025,"finding":"RPS27 acts as an RNA-binding protein in Kaposi's sarcoma cells and selectively binds a set of ribosomal protein mRNAs (including RPL8, RPL13, RPS2, RPS4X, RPS13, RPS18, RPS21, and others associated with viral transcription). RPS27 inhibition promotes cellular proliferation, migration, invasion, and angiogenesis of HUVECs.","method":"iRIP-seq (improved RNA immunoprecipitation sequencing), RNA-seq, siRNA knockdown, transwell migration/invasion assay, tube formation assay","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA-binding mapped by iRIP-seq combined with loss-of-function cellular phenotype, single lab","pmids":["40016701"],"is_preprint":false},{"year":2024,"finding":"RPS27 overexpression promotes prostate cancer liver metastasis in vivo, while RPS27 knockdown significantly reduces it. RPS27 promotes metastasis by selectively enhancing expression of genes involved in prostate cancer progression as revealed by mRNA sequencing.","method":"Intrasplenic xenograft injection (in vivo metastasis model), transwell migration/invasion assay, RPS27 overexpression and knockdown, mRNA sequencing","journal":"Cancer & metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo metastasis model with genetic gain- and loss-of-function, single lab","pmids":["38365771"],"is_preprint":false}],"current_model":"RPS27 (eS27/MPS-1) is a zinc finger-containing structural component of the 40S ribosomal subunit that, beyond its role in ribosome assembly and pre-rRNA processing, participates in extra-ribosomal functions: its N-terminal region binds the central acidic domain of MDM2 to compete with p53, inhibit p53 ubiquitination, and stabilize p53; it is itself stabilized by MDM2-mediated neddylation and destabilized by NEDP1; recurrent 5'UTR mutations in melanoma expand its 5'TOP regulatory element; Rps27-containing ribosomes preferentially translate specific mRNA subsets and are functionally interchangeable with Rps27l ribosomes provided total expression is maintained; and RPS27 directly contacts the MAP3K ZAKα at the ribosomal mRNA exit channel to participate in ribotoxic stress sensing."},"narrative":{"mechanistic_narrative":"RPS27 (eS27) is a zinc finger-containing structural protein of the 40S ribosomal small subunit, purified directly from ribosomes and required for normal pre-rRNA processing [PMID:947902, PMID:8441676, PMID:25424902]. Beyond its ribosomal role, its N-terminal region binds the central acidic domain of MDM2 to form an MDM2–p53 triplex, competing with p53 for MDM2, inhibiting p53 ubiquitination, and extending p53 half-life; p53 in turn represses RPS27 expression, defining a feedback loop [PMID:21170087]. RPS27 stability is itself controlled by post-translational modification: MDM2 neddylates RPS27 and NEDP1 deneddylates it, so that neddylation blockade shortens RPS27 half-life and modulates cancer-cell sensitivity to apoptosis [PMID:32779270]. Genetic studies establish RPS27 in ribosomopathy and translational specialization: a loss-of-function frameshift causes Diamond-Blackfan anaemia with impaired erythropoiesis [PMID:25424902], and Rps27- versus its paralog Rps27l-containing ribosomes preferentially translate distinct mRNA subsets yet are functionally interchangeable provided total expression is maintained [PMID:37306301]. RPS27 also acts as an mRNA-binding protein that selectively associates with a defined set of ribosomal-protein transcripts [PMID:40016701], and contacts the ribotoxic-stress kinase ZAKα at the ribosomal mRNA exit channel to participate in sensing translational impairment [PMID:bio_10.1101_2025.11.22.689755]. In cancer, RPS27 expression—altered by recurrent melanoma 5'UTR/promoter mutations—modulates proliferation, invasion, and metastatic capacity [PMID:24913145, PMID:31663663, PMID:38365771].","teleology":[{"year":1976,"claim":"Established RPS27 as a genuine structural subunit of the small ribosomal subunit rather than a contaminant, the foundation for all subsequent work.","evidence":"Biochemical purification from rat liver 40S subunits by chromatography and SDS-PAGE","pmids":["947902"],"confidence":"High","gaps":["Position within the assembled 40S and rRNA contacts not resolved","No functional role assigned beyond structural presence"]},{"year":1993,"claim":"Defined the primary structure and identified a C4-type zinc finger motif, raising the possibility of nucleic-acid interaction beyond a passive structural role.","evidence":"cDNA and amino acid sequencing of rat RPS27 plus metal-content analysis of ribosomes","pmids":["8441676"],"confidence":"Medium","gaps":["Zinc finger function not tested by mutagenesis","No demonstration of DNA/RNA binding through the motif at this stage"]},{"year":2010,"claim":"Revealed an extra-ribosomal function in which RPS27 stabilizes p53 by competing for MDM2, connecting a ribosomal protein to tumor-suppressor regulation.","evidence":"Reciprocal Co-IP, domain-mapping pulldowns, in vivo ubiquitination assay, and p53 half-life measurements with siRNA","pmids":["21170087"],"confidence":"High","gaps":["Whether free vs ribosome-bound RPS27 drives the interaction unclear","Structural basis of the N-terminus/MDM2 acidic-domain contact not defined"]},{"year":2014,"claim":"Linked RPS27 loss-of-function to Diamond-Blackfan anaemia and a defined pre-rRNA processing defect, establishing it as a ribosomopathy gene with erythroid relevance.","evidence":"Whole-exome sequencing of a patient, in vitro pre-rRNA processing assay, and zebrafish morpholino knockdown","pmids":["25424902"],"confidence":"Medium","gaps":["Specific pre-rRNA cleavage step affected not mapped","Mechanism linking processing defect to erythroid failure not established"]},{"year":2014,"claim":"Identified recurrent melanoma 5'UTR mutations that expand the 5'TOP element, implicating altered growth-dependent translational control of RPS27 in cancer.","evidence":"Exome sequencing of melanoma cohorts with 5'TOP element functional analysis","pmids":["24913145"],"confidence":"Medium","gaps":["Direct effect on RPS27 protein output in melanoma not quantified","Downstream oncogenic consequence not mechanistically traced"]},{"year":2019,"claim":"Showed RPS27 expression level functionally dictates melanoma cell behavior, with high RPS27 favoring proliferation/invasion and low RPS27 favoring survival and therapy resistance.","evidence":"Promoter mutation sequencing, reporter assays, and loss-of-function invasion/proliferation assays","pmids":["31663663"],"confidence":"Medium","gaps":["Molecular effectors of the phenotypic switch unknown","Whether effects are ribosomal or extra-ribosomal not distinguished"]},{"year":2020,"claim":"Defined neddylation as a post-translational switch controlling RPS27 stability, identifying MDM2 as writer and NEDP1 as eraser and linking RPS27 levels to apoptotic sensitivity.","evidence":"Neddylation assays, CHX-chase half-life measurement, knockdown/overexpression, and MLN4924 apoptosis assays","pmids":["32779270"],"confidence":"Medium","gaps":["Neddylation acceptor site(s) on RPS27 not mapped","Relationship between neddylation and the MDM2/p53 axis not resolved"]},{"year":2022,"claim":"Suggested RPS27 overexpression reshapes inflammatory/immune and apoptotic gene programs and alternative splicing in thyroid cancer.","evidence":"Overexpression RNA-seq with splicing analysis and qRT-PCR validation","pmids":["35546566"],"confidence":"Low","gaps":["Single overexpression transcriptomics study without direct binding or epistasis","No demonstration of direct regulation of the affected genes"]},{"year":2023,"claim":"Demonstrated that Rps27 and Rps27l mark specialized ribosomes translating distinct mRNA subsets yet are functionally interchangeable when total expression is balanced, clarifying paralog roles.","evidence":"Endogenous tagging, ribosome profiling, and genetic knockin rescue in mouse knockouts","pmids":["37306301"],"confidence":"High","gaps":["Mechanism conferring mRNA preference not defined","Whether specialization matters in human disease unresolved"]},{"year":2024,"claim":"Provided in vivo evidence that RPS27 levels drive prostate cancer liver metastasis through selective regulation of progression-associated genes.","evidence":"Intrasplenic xenograft metastasis model with gain/loss of function and mRNA sequencing","pmids":["38365771"],"confidence":"Medium","gaps":["Direct targets driving metastasis not validated","Distinction between translational and signaling mechanisms unclear"]},{"year":2025,"claim":"Mapped RPS27 as an mRNA-binding protein selectively associating with ribosomal-protein transcripts in Kaposi's sarcoma cells, expanding its RNA-regulatory repertoire.","evidence":"iRIP-seq, RNA-seq, and knockdown with migration/invasion/tube-formation assays","pmids":["40016701"],"confidence":"Medium","gaps":["Whether binding occurs as free protein or within ribosomes unknown","Functional consequence of binding each target transcript not dissected"]},{"year":2025,"claim":"Placed RPS27 at the ribosomal mRNA exit channel as a direct contact for the ribotoxic-stress kinase ZAKα, implicating it in sensing translational impairment.","evidence":"AlphaFold3 prediction, CLIP, and biochemical interaction assays (preprint)","pmids":["bio_10.1101_2025.11.22.689755"],"confidence":"Medium","gaps":["Single preprint not yet peer-reviewed","Contribution of RPS27 specifically (vs RACK1/18S) to ZAKα activation not isolated"]},{"year":null,"claim":"How RPS27's ribosomal, RNA-binding, and extra-ribosomal (p53/MDM2, ZAKα) functions are coordinated, and whether they share a structural basis, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of RPS27 in complex with MDM2 or ZAKα","Mechanistic link between neddylation, p53 stabilization, and translational specialization undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,0]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[10,7]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[1,6]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[2,5]}],"complexes":["40S ribosomal subunit"],"partners":["MDM2","NEDP1","ZAKALPHA","RACK1","RPS27L"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P42677","full_name":"Small ribosomal subunit protein eS27","aliases":["40S ribosomal protein S27","Metallopan-stimulin 1","MPS-1"],"length_aa":84,"mass_kda":9.5,"function":"Component of the small ribosomal subunit (PubMed:23636399, PubMed:8706699). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for proper rRNA processing and maturation of 18S rRNAs (PubMed:25424902). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797)","subcellular_location":"Cytoplasm; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/P42677/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RPS27"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RBM8A","stoichiometry":4.0},{"gene":"RPL5","stoichiometry":4.0},{"gene":"SRP72","stoichiometry":4.0},{"gene":"ATG13","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"NCAPH","stoichiometry":0.2},{"gene":"RBM42","stoichiometry":0.2},{"gene":"SRP19","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RPS27","total_profiled":1310},"omim":[{"mim_id":"619447","title":"FAMILY WITH SEQUENCE SIMILARITY 189, MEMBER B; FAM189B","url":"https://www.omim.org/entry/619447"},{"mim_id":"617409","title":"DIAMOND-BLACKFAN ANEMIA 17; DBA17","url":"https://www.omim.org/entry/617409"},{"mim_id":"617408","title":"DIAMOND-BLACKFAN ANEMIA 16; DBA16","url":"https://www.omim.org/entry/617408"},{"mim_id":"612055","title":"RIBOSOMAL PROTEIN S27-LIKE; RPS27L","url":"https://www.omim.org/entry/612055"},{"mim_id":"607526","title":"RIBOSOMAL PROTEIN L27; RPL27","url":"https://www.omim.org/entry/607526"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPS27"},"hgnc":{"alias_symbol":["MPS-1","MPS1","S27","eS27"],"prev_symbol":[]},"alphafold":{"accession":"P42677","domains":[{"cath_id":"2.20.25.100","chopping":"28-80","consensus_level":"high","plddt":94.4079,"start":28,"end":80}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P42677","model_url":"https://alphafold.ebi.ac.uk/files/AF-P42677-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P42677-F1-predicted_aligned_error_v6.png","plddt_mean":92.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPS27","jax_strain_url":"https://www.jax.org/strain/search?query=RPS27"},"sequence":{"accession":"P42677","fasta_url":"https://rest.uniprot.org/uniprotkb/P42677.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P42677/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P42677"}},"corpus_meta":[{"pmid":"21170087","id":"PMC_21170087","title":"Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a substrate and a regulator.","date":"2010","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/21170087","citation_count":115,"is_preprint":false},{"pmid":"25424902","id":"PMC_25424902","title":"Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.","date":"2014","source":"British journal of haematology","url":"https://pubmed.ncbi.nlm.nih.gov/25424902","citation_count":84,"is_preprint":false},{"pmid":"8441676","id":"PMC_8441676","title":"Zinc finger-like motifs in rat ribosomal proteins S27 and S29.","date":"1993","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/8441676","citation_count":75,"is_preprint":false},{"pmid":"947902","id":"PMC_947902","title":"The isolation of eukaryotic ribosomal proteins. The purification and characterization of the 40 S ribosomal subunit proteins S2, S3, S4, S5, S6, S7, S8, S9, S13, S23/S24, S27, and S28.","date":"1976","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/947902","citation_count":72,"is_preprint":false},{"pmid":"28242385","id":"PMC_28242385","title":"Aerobic and heterotrophic nitrogen removal by Enterobacter cloacae CF-S27 with efficient utilization of hydroxylamine.","date":"2017","source":"Bioresource technology","url":"https://pubmed.ncbi.nlm.nih.gov/28242385","citation_count":68,"is_preprint":false},{"pmid":"925037","id":"PMC_925037","title":"Isolation of eukaryotic ribosomal proteins. 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Isolation of proteins S8, S13, S14, S16, S19, S20/L24, S22/L26, S24, S25/S27, S26, S29, L4, L10/L11, L12, L13, L16, L18, L19, L27, 1, 7/8, 9, and 11.","date":"1980","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/6773542","citation_count":16,"is_preprint":false},{"pmid":"22798506","id":"PMC_22798506","title":"Increased serum level of RPMPS-1/S27 protein in patients with various types of cancer is useful for the early detection, prevention and therapy.","date":"2012","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/22798506","citation_count":15,"is_preprint":false},{"pmid":"31663663","id":"PMC_31663663","title":"Functional analysis of RPS27 mutations and expression in melanoma.","date":"2019","source":"Pigment cell & melanoma research","url":"https://pubmed.ncbi.nlm.nih.gov/31663663","citation_count":13,"is_preprint":false},{"pmid":"35427653","id":"PMC_35427653","title":"Identification of meroterpenoids from Bipolaris victoriae S27 and their potential activity against tumor metastasis and inhibition of the NF-κB signaling pathway.","date":"2022","source":"Phytochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35427653","citation_count":13,"is_preprint":false},{"pmid":"33051438","id":"PMC_33051438","title":"Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33051438","citation_count":12,"is_preprint":false},{"pmid":"31235856","id":"PMC_31235856","title":"A novel potent autophagy inhibitor ECDD-S27 targets vacuolar ATPase and inhibits cancer cell survival.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31235856","citation_count":12,"is_preprint":false},{"pmid":"31887531","id":"PMC_31887531","title":"Molecular cloning, expression and impact of ribosomal protein S-27 silencing in Haemaphysalis longicornis (Acari: Ixodidae).","date":"2019","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/31887531","citation_count":12,"is_preprint":false},{"pmid":"8908372","id":"PMC_8908372","title":"Primary structures and sequence analysis of human ribosomal proteins L39 and S27.","date":"1996","source":"Biochemistry and molecular biology international","url":"https://pubmed.ncbi.nlm.nih.gov/8908372","citation_count":10,"is_preprint":false},{"pmid":"37306301","id":"PMC_37306301","title":"Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/37306301","citation_count":9,"is_preprint":false},{"pmid":"38365771","id":"PMC_38365771","title":"High-fat diet promotes prostate cancer metastasis via RPS27.","date":"2024","source":"Cancer & 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MPS1 in Human Cerebellum.","date":"2016","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/26708598","citation_count":5,"is_preprint":false},{"pmid":"39467967","id":"PMC_39467967","title":"Impact of potential biomarkers, SNRPE, COX7C, and RPS27, on idiopathic Parkinson's disease.","date":"2024","source":"Genes & genomics","url":"https://pubmed.ncbi.nlm.nih.gov/39467967","citation_count":4,"is_preprint":false},{"pmid":"40280903","id":"PMC_40280903","title":"Single-cell multi-omics elucidates the role of RPS27-RPS24 fusion gene in osteosarcoma chemoresistance and metabolic regulation.","date":"2025","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/40280903","citation_count":3,"is_preprint":false},{"pmid":"2040456","id":"PMC_2040456","title":"Biochemical and genetic characterization of esterase-27 (ES-27), the major plasma cholinesterase of the house mouse (Mus musculus).","date":"1991","source":"Genetical research","url":"https://pubmed.ncbi.nlm.nih.gov/2040456","citation_count":3,"is_preprint":false},{"pmid":"40016701","id":"PMC_40016701","title":"Exploration of RNA-binding proteins identified RPS27 as a potential regulator associated with Kaposi's sarcoma development.","date":"2025","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/40016701","citation_count":2,"is_preprint":false},{"pmid":"31394666","id":"PMC_31394666","title":"Metallopanstimulin / S27 Ribosomal Antigen Expression in Stages I and II Breast Cancer: its Relationship with Clinicopathologic Factors.","date":"2005","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/31394666","citation_count":2,"is_preprint":false},{"pmid":"11253425","id":"PMC_11253425","title":"[Complementation analysis of mutants of the associative bacteria Azospirillum brasilense Sp245 and S27, defective in mobility and 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finger-like motif (C4-type), consistent with zinc-binding and potential DNA/RNA interaction. Ribosomes and ribosomal subunits were shown to contain zinc and iron.\",\n      \"method\": \"cDNA sequencing, amino acid sequence determination, hybridization analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 (structural/primary structure determination) / Weak — single lab, biochemical characterization without functional mutagenesis of the zinc finger\",\n      \"pmids\": [\"8441676\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1976,\n      \"finding\": \"RPS27 was isolated and purified from the 40S ribosomal subunit of rat liver ribosomes, establishing it as a bona fide structural component of the small ribosomal subunit.\",\n      \"method\": \"Ion exchange chromatography, gel filtration, SDS-PAGE, amino acid composition analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical purification and characterization from ribosomes, foundational work replicated in subsequent studies\",\n      \"pmids\": [\"947902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"RPS27 binds to the central acidic domain of MDM2 via its N-terminal region, forming an in vivo triplex with MDM2-p53. RPS27 competes with p53 for MDM2 binding, inhibits MDM2-mediated p53 ubiquitination, and increases p53 levels by extending p53 protein half-life. RPS27 expression is repressed by p53.\",\n      \"method\": \"Co-immunoprecipitation, domain-mapping pulldown, ubiquitination assay, siRNA knockdown, p53 half-life measurements, reporter assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vivo ubiquitination assay, domain mapping, and functional p53 half-life measurements in single study with multiple orthogonal methods\",\n      \"pmids\": [\"21170087\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Loss-of-function frameshift deletion in RPS27 was identified in a Diamond-Blackfan anaemia patient. In vitro knockdown of RPS27 disrupted pre-ribosomal RNA processing. Zebrafish rps27 morphants showed impaired erythrocyte production and developmental defects.\",\n      \"method\": \"Whole-exome sequencing, in vitro knockdown, pre-rRNA processing assay, zebrafish morpholino knockdown model\",\n      \"journal\": \"British journal of haematology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined pre-rRNA processing phenotype and in vivo zebrafish model, single lab\",\n      \"pmids\": [\"25424902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"A recurrent hotspot mutation in the 5' UTR of RPS27 (~10% of melanomas) expands the 5'TOP element, a regulatory motif that controls expression of ribosomal protein transcripts in a growth-dependent manner, potentially sensitizing RPS27 mRNA to growth-mediated translational regulation.\",\n      \"method\": \"Exome sequencing of melanoma cohorts, 5'TOP element functional analysis\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — recurrent mutation identified across independent cohorts with in vitro functional characterization of 5'TOP motif expansion\",\n      \"pmids\": [\"24913145\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Both RPS27 and RPS27L are subjected to neddylation by MDM2 E3 ubiquitin ligase, and deneddylation by NEDP1. Blockage of neddylation with MLN4924 destabilizes RPS27 by shortening its protein half-life. Knockdown of RPS27 sensitizes cancer cells to MLN4924-induced apoptosis, while ectopic RPS27 expression desensitizes cells.\",\n      \"method\": \"Neddylation assay, protein half-life measurement (CHX chase), siRNA knockdown, ectopic overexpression, apoptosis assay\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct neddylation biochemical assay with identified writer (MDM2) and eraser (NEDP1), single lab with multiple functional readouts\",\n      \"pmids\": [\"32779270\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Rps27 and Rps27l are paralogous ribosomal proteins that arose by vertebrate whole-genome duplication. They have inversely correlated expression across mouse cell types. Rps27- and Rps27l-containing ribosomes preferentially associate with different subsets of mRNAs (specialized ribosomes). Homozygous loss of either is lethal at different developmental stages, but expressing one protein from the other's locus fully rescues lethality, demonstrating the two proteins are functionally equivalent but must achieve appropriate total expression across cell types.\",\n      \"method\": \"Endogenous protein tagging, ribosome profiling/RNA association, genetic knockin rescue, mouse knockout studies\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — endogenous tagging, ribosome profiling, and definitive genetic rescue experiments with multiple orthogonal approaches in a single rigorous study\",\n      \"pmids\": [\"37306301\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZAKα (the ribotoxic stress response kinase) directly interacts with RPS27 at the mRNA exit channel of elongating ribosomes, as well as with RACK1 and 18S rRNA helix-26. This interaction is stabilized by mRNA stasis and is part of a mechanism by which ZAKα senses translational impairment to activate p38/JNK signaling.\",\n      \"method\": \"AlphaFold3 structural prediction, RNA crosslinking and immunoprecipitation (CLIP), biochemical interaction assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CLIP and structural prediction with functional validation, single preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.11.22.689755\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Two recurrent mutations in the RPS27 promoter were associated with decreased RPS27 mRNA levels in vitro in melanoma. Loss-of-function experiments showed that high RPS27 status provides increased proliferative and invasive capacities, while low RPS27 confers survival advantage under low attachment conditions and resistance to therapy.\",\n      \"method\": \"Targeted sequencing, in vitro reporter assay, loss-of-function (siRNA/shRNA), transwell invasion/proliferation assay\",\n      \"journal\": \"Pigment cell & melanoma research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — promoter functional assay combined with loss-of-function phenotypic characterization, single lab\",\n      \"pmids\": [\"31663663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RPS27 overexpression in thyroid cancer cells selectively regulates expression of inflammatory/immune response genes and alternative splicing of genes in the TRIF-dependent toll-like receptor signaling pathway and apoptotic process, as revealed by transcriptome analysis.\",\n      \"method\": \"RPS27 overexpression, RNA-seq transcriptomics, alternative splicing analysis, qRT-PCR validation\",\n      \"journal\": \"Advances in clinical and experimental medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single overexpression transcriptomics study without mechanistic follow-up of direct binding or pathway epistasis\",\n      \"pmids\": [\"35546566\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPS27 acts as an RNA-binding protein in Kaposi's sarcoma cells and selectively binds a set of ribosomal protein mRNAs (including RPL8, RPL13, RPS2, RPS4X, RPS13, RPS18, RPS21, and others associated with viral transcription). RPS27 inhibition promotes cellular proliferation, migration, invasion, and angiogenesis of HUVECs.\",\n      \"method\": \"iRIP-seq (improved RNA immunoprecipitation sequencing), RNA-seq, siRNA knockdown, transwell migration/invasion assay, tube formation assay\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA-binding mapped by iRIP-seq combined with loss-of-function cellular phenotype, single lab\",\n      \"pmids\": [\"40016701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPS27 overexpression promotes prostate cancer liver metastasis in vivo, while RPS27 knockdown significantly reduces it. RPS27 promotes metastasis by selectively enhancing expression of genes involved in prostate cancer progression as revealed by mRNA sequencing.\",\n      \"method\": \"Intrasplenic xenograft injection (in vivo metastasis model), transwell migration/invasion assay, RPS27 overexpression and knockdown, mRNA sequencing\",\n      \"journal\": \"Cancer & metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo metastasis model with genetic gain- and loss-of-function, single lab\",\n      \"pmids\": [\"38365771\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPS27 (eS27/MPS-1) is a zinc finger-containing structural component of the 40S ribosomal subunit that, beyond its role in ribosome assembly and pre-rRNA processing, participates in extra-ribosomal functions: its N-terminal region binds the central acidic domain of MDM2 to compete with p53, inhibit p53 ubiquitination, and stabilize p53; it is itself stabilized by MDM2-mediated neddylation and destabilized by NEDP1; recurrent 5'UTR mutations in melanoma expand its 5'TOP regulatory element; Rps27-containing ribosomes preferentially translate specific mRNA subsets and are functionally interchangeable with Rps27l ribosomes provided total expression is maintained; and RPS27 directly contacts the MAP3K ZAKα at the ribosomal mRNA exit channel to participate in ribotoxic stress sensing.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPS27 (eS27) is a zinc finger-containing structural protein of the 40S ribosomal small subunit, purified directly from ribosomes and required for normal pre-rRNA processing [#1, #0, #3]. Beyond its ribosomal role, its N-terminal region binds the central acidic domain of MDM2 to form an MDM2–p53 triplex, competing with p53 for MDM2, inhibiting p53 ubiquitination, and extending p53 half-life; p53 in turn represses RPS27 expression, defining a feedback loop [#2]. RPS27 stability is itself controlled by post-translational modification: MDM2 neddylates RPS27 and NEDP1 deneddylates it, so that neddylation blockade shortens RPS27 half-life and modulates cancer-cell sensitivity to apoptosis [#5]. Genetic studies establish RPS27 in ribosomopathy and translational specialization: a loss-of-function frameshift causes Diamond-Blackfan anaemia with impaired erythropoiesis [#3], and Rps27- versus its paralog Rps27l-containing ribosomes preferentially translate distinct mRNA subsets yet are functionally interchangeable provided total expression is maintained [#6]. RPS27 also acts as an mRNA-binding protein that selectively associates with a defined set of ribosomal-protein transcripts [#10], and contacts the ribotoxic-stress kinase ZAKα at the ribosomal mRNA exit channel to participate in sensing translational impairment [#7]. In cancer, RPS27 expression—altered by recurrent melanoma 5'UTR/promoter mutations—modulates proliferation, invasion, and metastatic capacity [#4, #8, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 1976,\n      \"claim\": \"Established RPS27 as a genuine structural subunit of the small ribosomal subunit rather than a contaminant, the foundation for all subsequent work.\",\n      \"evidence\": \"Biochemical purification from rat liver 40S subunits by chromatography and SDS-PAGE\",\n      \"pmids\": [\"947902\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Position within the assembled 40S and rRNA contacts not resolved\", \"No functional role assigned beyond structural presence\"]\n    },\n    {\n      \"year\": 1993,\n      \"claim\": \"Defined the primary structure and identified a C4-type zinc finger motif, raising the possibility of nucleic-acid interaction beyond a passive structural role.\",\n      \"evidence\": \"cDNA and amino acid sequencing of rat RPS27 plus metal-content analysis of ribosomes\",\n      \"pmids\": [\"8441676\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Zinc finger function not tested by mutagenesis\", \"No demonstration of DNA/RNA binding through the motif at this stage\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Revealed an extra-ribosomal function in which RPS27 stabilizes p53 by competing for MDM2, connecting a ribosomal protein to tumor-suppressor regulation.\",\n      \"evidence\": \"Reciprocal Co-IP, domain-mapping pulldowns, in vivo ubiquitination assay, and p53 half-life measurements with siRNA\",\n      \"pmids\": [\"21170087\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether free vs ribosome-bound RPS27 drives the interaction unclear\", \"Structural basis of the N-terminus/MDM2 acidic-domain contact not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linked RPS27 loss-of-function to Diamond-Blackfan anaemia and a defined pre-rRNA processing defect, establishing it as a ribosomopathy gene with erythroid relevance.\",\n      \"evidence\": \"Whole-exome sequencing of a patient, in vitro pre-rRNA processing assay, and zebrafish morpholino knockdown\",\n      \"pmids\": [\"25424902\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific pre-rRNA cleavage step affected not mapped\", \"Mechanism linking processing defect to erythroid failure not established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified recurrent melanoma 5'UTR mutations that expand the 5'TOP element, implicating altered growth-dependent translational control of RPS27 in cancer.\",\n      \"evidence\": \"Exome sequencing of melanoma cohorts with 5'TOP element functional analysis\",\n      \"pmids\": [\"24913145\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct effect on RPS27 protein output in melanoma not quantified\", \"Downstream oncogenic consequence not mechanistically traced\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed RPS27 expression level functionally dictates melanoma cell behavior, with high RPS27 favoring proliferation/invasion and low RPS27 favoring survival and therapy resistance.\",\n      \"evidence\": \"Promoter mutation sequencing, reporter assays, and loss-of-function invasion/proliferation assays\",\n      \"pmids\": [\"31663663\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular effectors of the phenotypic switch unknown\", \"Whether effects are ribosomal or extra-ribosomal not distinguished\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined neddylation as a post-translational switch controlling RPS27 stability, identifying MDM2 as writer and NEDP1 as eraser and linking RPS27 levels to apoptotic sensitivity.\",\n      \"evidence\": \"Neddylation assays, CHX-chase half-life measurement, knockdown/overexpression, and MLN4924 apoptosis assays\",\n      \"pmids\": [\"32779270\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Neddylation acceptor site(s) on RPS27 not mapped\", \"Relationship between neddylation and the MDM2/p53 axis not resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Suggested RPS27 overexpression reshapes inflammatory/immune and apoptotic gene programs and alternative splicing in thyroid cancer.\",\n      \"evidence\": \"Overexpression RNA-seq with splicing analysis and qRT-PCR validation\",\n      \"pmids\": [\"35546566\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single overexpression transcriptomics study without direct binding or epistasis\", \"No demonstration of direct regulation of the affected genes\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated that Rps27 and Rps27l mark specialized ribosomes translating distinct mRNA subsets yet are functionally interchangeable when total expression is balanced, clarifying paralog roles.\",\n      \"evidence\": \"Endogenous tagging, ribosome profiling, and genetic knockin rescue in mouse knockouts\",\n      \"pmids\": [\"37306301\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism conferring mRNA preference not defined\", \"Whether specialization matters in human disease unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided in vivo evidence that RPS27 levels drive prostate cancer liver metastasis through selective regulation of progression-associated genes.\",\n      \"evidence\": \"Intrasplenic xenograft metastasis model with gain/loss of function and mRNA sequencing\",\n      \"pmids\": [\"38365771\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct targets driving metastasis not validated\", \"Distinction between translational and signaling mechanisms unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Mapped RPS27 as an mRNA-binding protein selectively associating with ribosomal-protein transcripts in Kaposi's sarcoma cells, expanding its RNA-regulatory repertoire.\",\n      \"evidence\": \"iRIP-seq, RNA-seq, and knockdown with migration/invasion/tube-formation assays\",\n      \"pmids\": [\"40016701\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether binding occurs as free protein or within ribosomes unknown\", \"Functional consequence of binding each target transcript not dissected\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed RPS27 at the ribosomal mRNA exit channel as a direct contact for the ribotoxic-stress kinase ZAKα, implicating it in sensing translational impairment.\",\n      \"evidence\": \"AlphaFold3 prediction, CLIP, and biochemical interaction assays (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.11.22.689755\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single preprint not yet peer-reviewed\", \"Contribution of RPS27 specifically (vs RACK1/18S) to ZAKα activation not isolated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPS27's ribosomal, RNA-binding, and extra-ribosomal (p53/MDM2, ZAKα) functions are coordinated, and whether they share a structural basis, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of RPS27 in complex with MDM2 or ZAKα\", \"Mechanistic link between neddylation, p53 stabilization, and translational specialization undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 0]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [10, 7]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [1, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [2, 5]}\n    ],\n    \"complexes\": [\n      \"40S ribosomal subunit\"\n    ],\n    \"partners\": [\n      \"MDM2\",\n      \"NEDP1\",\n      \"ZAKalpha\",\n      \"RACK1\",\n      \"RPS27L\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}